NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp) AND Diabetes mellitus, transient neonatal, 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 24, 2014
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000192916.9

Allele description [Variation Report for NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)]

NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)

HGVS:

NC_000011.10:g.17404525G>A
NG_008867.1:g.77378C>T
NM_000352.6:c.3544C>TMANE SELECT
NM_001287174.3:c.3547C>T
NM_001351295.2:c.3610C>T
NM_001351296.2:c.3544C>T
NM_001351297.2:c.3541C>T
NP_000343.2:p.Arg1182Trp
NP_001274103.1:p.Arg1183Trp
NP_001338224.1:p.Arg1204Trp
NP_001338225.1:p.Arg1182Trp
NP_001338226.1:p.Arg1181Trp
LRG_790t1:c.3544C>T
LRG_790t2:c.3547C>T
LRG_790:g.77378C>T
LRG_790p1:p.Arg1182Trp
LRG_790p2:p.Arg1183Trp
NC_000011.9:g.17426072G>A
NM_000352.3:c.3544C>T
NM_000352.5:c.3544C>T
NR_147094.2:n.3693C>T

Protein change:

R1181W; ARG1182TRP

Links:

OMIM: 600509.0031; dbSNP: rs797045209

NCBI 1000 Genomes Browser:

rs797045209

Molecular consequence:

NM_000352.6:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3610C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3541C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3693C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Diabetes mellitus, transient neonatal, 2 (TNDM2)
Identifiers:: MONDO: MONDO:0012480; MedGen: C1835887; Orphanet: 99886; OMIM: 610374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000246296	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 24, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV006076849	OMIM	no assertion criteria provided	Pathogenic (May 9, 2025)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000246296

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 24, 2014)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV006076849

OMIM

no assertion criteria provided

Pathogenic
(May 9, 2025)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications.

Timmers M, Dirinck E, Lauwers P, Wuyts W, De Block C.

Diabetes Metab Res Rev. 2021 Nov;37(8):e3459. doi: 10.1002/dmrr.3459. Epub 2021 May 20.

PubMed [citation]

PMID:: 34014594

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000246296.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From OMIM, SCV006076849.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 35-year-old woman with maturity-onset diabetes of the young-12 (MODY12; 621196) who had severe microvascular diabetic complications, Timmers et al. (2021) identified heterozygosity for a c.3544C-T transition (c.3544C-T, NM_000352.6) in the ABCC8 gene that resulted in an arg1182-to-trp (R1182W) substitution. The mutation was present in 1/152,080 alleles in the gnomAD (v3.1) database. The mutation was subsequently identified in her mother, older daughter, and son. Her mother had diabetes which required only oral agents, and neither of her children had had neonatal diabetes. Timmers et al. (2021) noted that 2 transcripts for the ABCC8 gene differing in length by 1 amino acid arise by alternative splicing at exon 17; thus, residue R1182 may be referred to as R1183 according to another reference sequence.

Timmers et al. (2021) identified 10 reports in the literature that included individuals with the R1182W mutation, with phenotypes of transient neonatal diabetes mellitus (TNDM2; 610374), permanent neonatal diabetes permanent neonatal diabetes mellitus (PNDM3; 618857), and MODY. Patients were responsive to sulfonylurea.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 22, 2025

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